title: Outer membrane vesicles from pathogenic bacteria initiate an inflammatory response in human endothelial cells.
abstract: BACKGROUND
  Gram-negative bacteria release outer membrane vesicles (OMVs) during growth that contain various membrane components involved in eliciting an inflammatory response, including lipopolysaccharide and virulence factors. However, little is known about the role of OMVs in sepsis. The objective of this study was to determine how OMVs, derived from Escherichia (E.) coli, elicit the cellular responses involved in activating the inflammatory cascade, and to determine whether additional virulence factors in pathogenic OMVs augment the inflammatory response.
  
  
  METHODS
  Human umbilical endothelial cells were inoculated with OMVs from non-pathogenic E. coli (npOMV) or pathogenic E. coli (pOMV) and analyzed for adhesion protein synthesis, cytokine production, and necrosis factor (NF)-κB translocation.
  
  
  RESULTS
  Flow cytometry demonstrated that human umbilical vein endothelial cells exposed to npOMV or pOMV significantly increased expression of E-selectin and intercellular adhesion molecule, with a large population of cells demonstrating increased expression of both proteins. Interleukin-6 levels were significantly elevated by 4 h after exposure to npOMV and pOMVs. NF-κB translocation to the nucleus was shown to be induced by npOMV and pOMVs. However, the role of additional virulence factors associated with pOMVs remains undefined.
  
  
  CONCLUSIONS
  Both npOMVs and pOMVs are capable of initiating the inflammatory cascade in endothelial cells. OMVs trigger NF-κB translocation to the nucleus, resulting in up-regulation of adhesion molecules and cytokines, presumably for the recruitment of leukocytes. By eliciting an inflammatory response, OMVs could facilitate the transition from a localized infection to a systemic response, and ultimately sepsis.
authors.affiliation: Department of Surgery, Eastern Virginia Medical School, Norfolk, Virginia 23501, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Soult
authors.forename: Natalie E
authors.initials: NE
authors.lastname: Lonergan
authors.forename: Bhairav
authors.initials: B
authors.lastname: Shah
authors.forename: Woong-Ki
authors.initials: WK
authors.lastname: Kim
authors.forename: L D
authors.initials: LD
authors.lastname: Britt
authors.forename: Claretta J
authors.initials: CJ
authors.lastname: Sullivan
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D021961:Cell Membrane Structures / Q000276:immunology* / Q000382:microbiology; D042783:Endothelial Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D004926:Escherichia coli / Q000276:immunology* / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000276:immunology*; D010861:Fimbriae, Bacterial / Q000276:immunology; D005434:Flow Cytometry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D018805:Sepsis / Q000276:immunology / Q000382:microbiology; D037521:Virulence Factors / Q000276:immunology
chemical_list: D001425:Bacterial Outer Membrane Proteins; D015815:Cell Adhesion Molecules; C508600:IL6 protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D037521:Virulence Factors
keywords: E-selectin; Endothelium; IL-6; NF-κB; Outer membrane vesicles; Sepsis